Predicting risk of dementia among the elderly with major depressive disorder in remission: A prospective study.

OBJECTIVES: Cognitive impairment and change are a focus of research into late-life depression. The aims of this 5-year prospective study were (1) to observe cognitive status change; (2) to investigate the rate and risk ratio of dementia or cognitive decline; and (3) to examine the cognitive domain predictors for conversion to dementia within 5 years among a clinical cohort with remitted major depressive disorder (MDD). METHODS: The study cohort included 130 elderly persons with late-life remitted MDD and 100 normal controls. Comprehensive neuropsychological tests were conducted to determine cognitive domain status. Diagnoses of mild cognitive impairment (MCI) and dementia were made at baseline and at a follow-up visit at the 5-year point. In total, 98 cases and 55 normal controls completed the 5-year follow-up assessment. RESULTS: Of the study cohort with late-life remitted MDD, 28.6% had MCI and 25.5% developed dementia within 5 years. Patients with late-life remitted MDD had an approximate 3 times higher risk of subsequent cognitive decline as compared with the normal controls. Information-processing speed (p = 0.009) and memory (p = 0.041) could predict subsequent progression to dementia within 5 years among patients with MDD. CONCLUSIONS: This study demonstrated that compared with the general elderly population, elderly patients with depression have more significant impairment in cognitive function after 5 years. Further, we found that in depressed patients, deficits in information-processing speed and memory domains were highly suggestive of progression to dementia within 5 years.

Application of blood-based biomarkers of Alzheimer's disease in clinical practice: Recommendations from Taiwan Dementia Society.

Blood-based biomarkers (BBM) are potentially powerful tools that assist in the biological diagnosis of Alzheimer's disease (AD) in vivo with minimal invasiveness, relatively low cost, and good accessibility. This review summarizes current evidence for using BBMs in AD, focusing on amyloid, tau, and biomarkers for neurodegeneration. Blood-based phosphorylated tau and the Aß42/Aß40 ratio showed consistent concordance with brain pathology measured by CSF or PET in the research setting. In addition, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are neurodegenerative biomarkers that show the potential to assist in the differential diagnosis of AD. Other pathology-specific biomarkers, such as α-synuclein and TAR DNA-binding protein 43 (TDP-43), can potentially detect AD concurrent pathology. Based on current evidence, the working group from the Taiwan Dementia Society (TDS) achieved consensus recommendations on the appropriate use of BBMs for AD in clinical practice. BBMs may assist clinical diagnosis and prognosis in AD subjects with cognitive symptoms; however, the results should be interpreted by dementia specialists and combining biochemical, neuropsychological, and neuroimaging information. Further studies are needed to evaluate BBMs' real-world performance and potential impact on clinical decision-making.

Stimulation of naïve B cells with a fusion protein consisting of FlaA and Bet v 1 induces regulatory B cells ex vivo.

BACKGROUND: The experimental fusion protein rFlaA:Betv1 was shown to efficiently suppress allergen-specific sensitization in mice. However, the detailed mechanism of rFlaA:Betv1-mediated immune modulation is not fully understood. In this study, we investigated the effect of rFlaA:Betv1 on naïve murine B cells. METHODS: Immune modulating capacity of rFlaA:Betv1 was screened in IL-10 reporter mice. B cells were isolated from spleens of naïve C57Bl/6, TLR5-/- , or MyD88-/- mice, stimulated with rFlaA:Betv1 and controls, and monitored for the expression of the regulatory B cell markers CD1d, CD24, CD38, and surface IgM by flow cytometry. Secreted cytokines, antibodies, and reactivity of the induced antibodies were investigated by ELISA and intracellular flow cytometry. Suppressive capacity of rFlaA:Betv1-stimulated B cells was tested in mDC:CD4+ T cell:B cell triple cultures. RESULTS: Upon in vivo application of rFlaA:Betv1 into IL-10-GFP reporter mice, CD19+ B cells were shown to produce anti-inflammatory IL-10, suggesting B cells to contribute to the immune-modulatory properties of rFlaA:Betv1. rFlaA:Betv1-induced IL-10 secretion was confirmed in human B cells isolated from buffy coats. In vitro stimulation of naïve murine B cells with rFlaA:Betv1 resulted in an mTOR- and MyD88-dependent production of IL-10 and rFlaA:Betv1 induced Bet v 1-reactive IgG production, which was not observed for IgA. rFlaA:Betv1-stimulated B cells formed a CD19+ CD24+ CD1d+ IgM+ CD38+ Breg subpopulation capable of suppressing Bet v 1-induced TH2 cytokine secretion in vitro. CONCLUSION: rFlaA:Betv1 can act as a thymus-independent B cell antigen, stimulating the mTOR- and MyD88-dependent differentiation of B cells displaying a regulatory phenotype, IL-10 secretion, antigen-binding antibody production, and a suppressive capacity in vitro.

Role of Glycolysis and Fatty Acid Synthesis in the Activation and T Cell-Modulating Potential of Dendritic Cells Stimulated with a TLR5-Ligand Allergen Fusion Protein.

Trained immune responses, based on metabolic and epigenetic changes in innate immune cells, are de facto innate immune memory and, therefore, are of great interest in vaccine development. In previous studies, the recombinant fusion protein rFlaA:Betv1, combining the adjuvant and toll-like receptor (TLR)5-ligand flagellin (FlaA) and the major birch pollen allergen Bet v 1 into a single molecule, significantly suppressed allergic sensitization in vivo while also changing the metabolism of myeloid dendritic cells (mDCs). Within this study, the immune-metabolic effects of rFlaA:Betv1 during mDC activation were elucidated. In line with results for other well-characterized TLR-ligands, rFlaA:Betv1 increased glycolysis while suppressing oxidative phosphorylation to different extents, making rFlaA:Betv1 a suitable model to study the immune-metabolic effects of TLR-adjuvanted vaccines. In vitro pretreatment of mDCs with cerulenin (inhibitor of fatty acid biosynthesis) led to a decrease in both rFlaA:Betv1-induced anti-inflammatory cytokine Interleukin (IL) 10 and T helper cell type (TH) 1-related cytokine IL-12p70, while the pro-inflammatory cytokine IL 1ß was unaffected. Interestingly, pretreatment with the glutaminase inhibitor BPTES resulted in an increase in IL-1ß, but decreased IL-12p70 secretion while leaving IL-10 unchanged. Inhibition of the glycolytic enzyme hexokinase-2 by 2-deoxyglucose led to a decrease in all investigated cytokines (IL-10, IL-12p70, and IL-1ß). Inhibitors of mitochondrial respiration had no effect on rFlaA:Betv1-induced IL-10 level, but either enhanced the secretion of IL-1ß (oligomycin) or decreased IL-12p70 (antimycin A). In extracellular flux measurements, mDCs showed a strongly enhanced glycolysis after rFlaA:Betv1 stimulation, which was slightly increased after respiratory shutdown using antimycin A. rFlaA:Betv1-stimulated mDCs secreted directly antimicrobial substances in a mTOR- and fatty acid metabolism-dependent manner. In co-cultures of rFlaA:Betv1-stimulated mDCs with CD4+ T cells, the suppression of Bet v 1-specific TH2 responses was shown to depend on fatty acid synthesis. The effector function of rFlaA:Betv1-activated mDCs mainly relies on glycolysis, with fatty acid synthesis also significantly contributing to rFlaA:Betv1-mediated cytokine secretion, the production of antimicrobial molecules, and the modulation of T cell responses.

Immune metabolism in allergies, does it matter?-A review of immune metabolic basics and adaptations associated with the activation of innate immune cells in allergy.

Type I allergies are pathological, type 2 inflammatory immune responses against otherwise harmless environmental allergens that arise from complex interactions between different types of immune cells. Activated immune cells undergo extensive changes in phenotype and function to fulfill their effector functions. Hereby, activation, differentiation, proliferation, migration, and mounting of effector responses require metabolic reprogramming. While the metabolic changes associated with activation of dendritic cells, macrophages, and T cells are extensively studied, data about the metabolic phenotypes of the other cell types critically involved in allergic responses (epithelial cells, eosinophils, basophils, mast cells, and ILC2s) are rather limited. This review briefly covers the basics of cellular energy metabolism and its connection to immune cell function. In addition, it summarizes the current state of knowledge in terms of dendritic cell and macrophage metabolism and subsequently focuses on the metabolic changes associated with activation of epithelial cells, eosinophils, basophils, mast cells, as well as ILC2s in allergy. Interestingly, the innate key cell types in allergic inflammation were reported to change their metabolic phenotype during activation, shifting to either glycolysis (epithelial cells, M1 macrophages, DCs, eosinophils, basophils, acutely activated mast cells), oxidative phosphorylation (M2 macrophages, longer term activated mast cells), or fatty acid oxidation (ILC2s). Therefore, immune metabolism is of relevance in allergic diseases and its connection to immune cell effector function needs to be considered to better understand induction and maintenance of allergic responses. Further progress in this field will likely improve both our understanding of disease pathology and enable new treatment targets/strategies.

Heterodyne terahertz detection through electronic and optoelectronic mixers.

The high sensitivity detection of terahertz radiation is crucial for many chemical sensing, biomedical imaging, security screening, nondestructive quality control, high-data-rate communication, atmospheric, and astrophysics sensing applications. Among various terahertz detection techniques, heterodyne detection is of great interest for applications that require high spectral resolution. Heterodyne detection involves mixing the received terahertz radiation with a reference terahertz signal provided by a local oscillator and then down-converting it to an intermediate frequency for detection. The frequency of the intermediate frequency signal is usually chosen to be in the radio frequency regime, so that it can be accurately analyzed by well-developed radio frequency electronics, including amplifiers, filters, and spectrometers, for further processing. Heterodyne terahertz detection offers two major advantages over direct terahertz detection. First, the detected terahertz radiation is effectively enhanced by the reference local oscillator signal through the mixing process, thereby enabling the detection of very weak terahertz signals. Second, the detected noise power is effectively reduced by limiting the detected spectral bandwidth to the bandwidth of the intermediate frequency electronics. In this article, we present a broad overview of various types of heterodyne terahertz receivers, which utilize different electronic and optoelectronic techniques to down-convert the received terahertz signal to a radio frequency signal. We describe how the inherent nonlinearity of a Schottky diode, superconductor-insulator-superconductor junction, hot electron bolometer, and field-effect transistor can be utilized to mix the received terahertz radiation with a reference local oscillator signal from a gas laser, quantum cascade laser, photomixer, Gunn diode, IMPATT diode, and frequency multiplier and then down-convert it to a radio frequency signal. The down-converted radio frequency signal can be subsequently detected and analyzed by various backend spectrometers, including filter bank, acousto-optical, autocorrelator, fast Fourier transform, and chirp transform spectrometers. We also discuss how a photomixer pumped by a heterodyning optical beam can be used to down-convert the received terahertz radiation to a radio frequency signal with far fewer bandwidth constraints than conventional techniques. The advantages and disadvantages of different heterodyne receivers in terms of their noise performance, operation frequency, operation bandwidth, and operation temperature are discussed in detail.

Bidirectional relationships of psychiatric symptoms with internet addiction in college students: A prospective study.

BACKGROUND/PURPOSE: This prospective study evaluated the predictive ability of psychiatric symptoms at initial consultation for the occurrence and remission of Internet addiction during a 1-year follow-up period among college students. Furthermore, it evaluated the predictive ability of changes in psychiatric symptoms for Internet addiction at the initial consultation during the 1-year follow-up period among college students. METHODS: Five hundred college students (262 women and 238 men) were recruited. The baseline and follow-up consultations measured the levels of Internet addiction and psychiatric symptoms using the Chen Internet Addiction Scale and Symptom Checklist-90 Revised, respectively. RESULTS: The results indicated that severe interpersonal sensitivity and paranoia symptoms might predict the incidence of Internet addiction at 1-year follow-up. The college students with internet addiction did not have significant improvement in the severities of psychopathology, whereas those without internet addiction had significant improvement in obsession-compulsion, interpersonal sensitivity, paranoid and psychoticism during the same period. CONCLUSION: Psychiatric symptoms and Internet addiction exhibited bidirectional relationships in college students during the 1-year follow-up period.

Plasmonic heterodyne spectrometry for resolving the spectral signatures of ammonia over a 1-4.5 THz frequency range.

We present a heterodyne terahertz spectrometry platform based on plasmonic photomixing, which enables the resolution of narrow spectral signatures of gases over a broad terahertz frequency range. This plasmonic heterodyne spectrometer replaces the terahertz mixer and local oscillator of conventional heterodyne spectrometers with a plasmonic photomixer and a heterodyning optical pump beam, respectively. The heterodyning optical pump beam is formed by two continuous-wave, wavelength-tunable lasers with a broadly tunable terahertz beat frequency. This broadly tunable terahertz beat frequency enables spectrometry over a broad bandwidth, which is not restricted by the bandwidth limitations of conventional terahertz mixers and local oscillators. We use this plasmonic heterodyne spectrometry platform to resolve the spectral signatures of ammonia over a 1-4.5 THz frequency range.

Autophagy suppresses tumorigenesis of hepatitis B virus-associated hepatocellular carcinoma through degradation of microRNA-224.

UNLABELLED: In hepatocellular carcinoma (HCC), dysregulated expression of microRNA-224 (miR-224) and impaired autophagy have been reported separately. However, the relationship between them has not been explored. In this study we determined that autophagy is down-regulated and inversely correlated with miR-224 expression in hepatitis B virus (HBV)-associated HCC patient specimens. These results were confirmed in liver tumors of HBV X gene transgenic mice. Furthermore, miR-224 was preferentially recruited and degraded during autophagic progression demonstrated by real-time polymerase chain reaction and miRNA in situ hybridization electron microscopy after extraction of autophagosomes. Our in vitro study demonstrated that miR-224 played an oncogenic role in hepatoma cell migration and tumor formation through silencing its target gene Smad4. In HCC patients, the expression of low-Atg5, high-miR-224, and low-Smad4 showed significant correlation with HBV infection and a poor overall survival rate. Autophagy-mediated miR-224 degradation and liver tumor suppression were further confirmed by the autophagy inducer amiodarone and miR-224 antagonist using an orthotopic SD rat model. CONCLUSION: A noncanonical pathway links autophagy, miR-224, Smad4, and HBV-associated HCC. These findings open a new avenue for the treatment of HCC.

Road traffic noise frequency and prevalent hypertension in Taichung, Taiwan: a cross-sectional study.

BACKGROUND: Epidemiological studies have reported the association between hypertension and exposure to road traffic noise, but the association between noise frequency characteristics is not clear. This study investigated the association between exposure to different frequency components of road traffic noise and the prevalence of hypertension in central Taiwan. METHODS: We recruited 820 residents living near main roads for more than 3 years. Frequency components of traffic noise and traffic flow rates during 0900-1700 on weekdays were measured simultaneously in 2008. Multiple logistic regressions were conducted to estimate odds ratios (ORs) for diagnosed hypertension, adjusting for potential confounders and the total traffic flow rate. RESULTS: The high-exposure group (≥ the median of noise levels [decibels, dB]) at 63 Hz, 125 Hz and 1000 Hz had ORs for hypertension of 2.77 (95% confidence interval [CI]: 1.17-6.52), 4.08 (95% CI: 1.57-10.63) and 1.98 (1.00-3.92) (95% CI: 1.00-3.92), respectively, compared to the low-exposure group (< the median of noise levels [dB]). There was an increasing trend in the prevalence of hypertension by exposure to road traffic noise at 63, 125 and 1000 Hz in all subjects and in men. Total subjects exposed to ≥ 51 dB at 125 Hz had an OR of 4.65 (95% CI = 1.46-14.83) compared to those exposed to < 47 dB. CONCLUSIONS: With the possible bias of exposure misclassification and a bias from using diagnosed hypertension, these results suggest that exposure to road traffic noise at low and hearing-sensitive frequencies may be associated with hypertension and exposure to noise at 125 Hz may have the greatest risk for hypertension.

Novel adjuvants in allergen-specific immunotherapy: where do we stand?

Type I hypersensitivity, or so-called type I allergy, is caused by Th2-mediated immune responses directed against otherwise harmless environmental antigens. Currently, allergen-specific immunotherapy (AIT) is the only disease-modifying treatment with the potential to re-establish clinical tolerance towards the corresponding allergen(s). However, conventional AIT has certain drawbacks, including long treatment durations, the risk of inducing allergic side effects, and the fact that allergens by themselves have a rather low immunogenicity. To improve AIT, adjuvants can be a powerful tool not only to increase the immunogenicity of co-applied allergens but also to induce the desired immune activation, such as promoting allergen-specific Th1- or regulatory responses. This review summarizes the knowledge on adjuvants currently approved for use in human AIT: aluminum hydroxide, calcium phosphate, microcrystalline tyrosine, and MPLA, as well as novel adjuvants that have been studied in recent years: oil-in-water emulsions, virus-like particles, viral components, carbohydrate-based adjuvants (QS-21, glucans, and mannan) and TLR-ligands (flagellin and CpG-ODN). The investigated adjuvants show distinct properties, such as prolonging allergen release at the injection site, inducing allergen-specific IgG production while also reducing IgE levels, as well as promoting differentiation and activation of different immune cells. In the future, better understanding of the immunological mechanisms underlying the effects of these adjuvants in clinical settings may help us to improve AIT.

Label-Free Optical Mapping for Large-Area Biomechanical Dynamics of Multicellular Systems.

Mapping cellular activities over large areas is crucial for understanding the collective behaviors of multicellular systems. Biomechanical properties, such as cellular traction force, serve as critical regulators of physiological states and molecular configurations. However, existing technologies for mapping large-area biomechanical dynamics are limited by the small field of view and scanning nature. To address this, we propose a novel platform that utilizes a vast number of optical diffractive elements for mapping large-area biomechanical dynamics. This platform achieves a field-of-view of 10.6 mm X 10.6 mm, a three-orders-of-magnitude improvement over traditional traction force microscopy. Transient mechanical waves generated by monolayer neonatal rat ventricular myocytes were captured with high spatiotemporal resolution (130 fps and 20 µm for temporal and spatial resolution, respectively). Furthermore, its label-free nature allows for long-term observations extended to a week, with minimal disruption of cellular functions. Finally, simultaneous measurements of calcium ions concentrations and biomechanical dynamics are demonstrated.

Massive field-of-view sub-cellular traction force videography enabled by Single-Pixel Optical Tracers (SPOT).

We report a massive field-of-view and high-speed videography platform for measuring the sub-cellular traction forces of more than 10,000 biological cells over 13 mm2 at 83 frames per second. Our Single-Pixel Optical Tracers (SPOT) tool uses 2-dimensional diffraction gratings embedded into a soft substrate to convert cells' mechanical traction force into optical colors detectable by a video camera. The platform measures the sub-cellular traction forces of diverse cell types, including tightly connected tissue sheets and near isolated cells. We used this platform to explore the mechanical wave propagation in a tightly connected sheet of Neonatal Rat Ventricular Myocytes (NRVMs) and discovered that the activation time of some tissue regions are heterogeneous from the overall spiral wave behavior of the cardiac wave.

Awareness and utilization of preventive care services among the elderly under National Health Insurance.

This empirical study investigates the factors affecting the awareness and the utilization of preventive care among the elderly in Taiwan. We use data obtained from the 2005 National Health Interview Survey. A recursive bivariate probit model is adopted to analyze the factors affecting the awareness and the utilization of preventive care. The probability of awareness of free preventive care under the National Health Insurance is higher for those who are younger, Mainlanders, have received more education, have a spouse, exercise regularly, have better self-rated health status, and have chronic diseases; the probability of awareness is lower for those who are aborigines and who live in the south and the east. Awareness of preventive care services, having a spouse, living alone, having better health status, and the existence of chronic diseases increase the probability of preventive care utilization; working reduces the probability of preventive care utilization. Our result supports the views in Arrow (Am Econ Rev 53(5):941-973, 1963) that health information is an important factor determining the demand for medical care. Policymakers may enhance such preventive care service utilization by increasing the awareness of such services among the elderly.

Predicting the Influences of Depression and Sexual Stigma on Motivation to Get Vaccinated against COVID-19 in Lesbian, Gay, and Bisexual Young Adults: A 4-Year Follow-Up Study.

Vaccination is a crucial preventive measure against COVID-19. However, limited research has focused on identifying the factors predicting motivation to get vaccinated against COVID-19 (MoVAC-19) among lesbian, gay, and bisexual (LGB) individuals. This study examined the predictive effects of depression and sexual stigma (i.e., perceived sexual stigma from family members, perceived sexual orientation microaggression, and internalized sexual stigma) before the COVID-19 pandemic on MoVAC-19 among LGB individuals 4 years later during the COVID-19 pandemic in Taiwan. Baseline data related to depression and sexual stigma were collected in 2018 and 2019. Depression was assessed using the 20-item Mandarin Chinese version of the Center for Epidemiologic Studies Depression Scale. Perceived sexual stigma from family members was assessed using the Homosexuality-Related Stigma Scale. Internalized sexual stigma was assessed using the Measure of Internalized Sexual Stigma for Lesbians and Gay Men. Perceived sexual orientation microaggression was assessed using the Sexual Orientation Microaggression Inventory. Participant MoVAC-19 during the pandemic was assessed using the nine-item Motors of COVID-19 Vaccination Acceptance Scale. The associations of depression and sexual stigma at baseline with MoVAC-19 at follow-up were examined through multivariate linear regression analysis. Internalized sexual stigma was negatively associated with MoVAC-19, whereas perceived sexual orientation microaggression was positively associated with MoVAC-19. Depression and perceived sexual stigma from family members were not significantly associated with MoVAC-19. Although male sex and older age were positively associated with increased MoVAC-19, sex and age did not moderate the relationship between sexual stigma and motivation to get vaccinated. Among LGB individuals, sexual stigma experiences should be considered when developing intervention strategies aimed at enhancing MoVAC-19.

Circadian typologies and insomnia in individuals with internet gaming disorder comorbid with attention deficit/hyperactivity disorder.

The alteration in circadian typology and insomnia were prevalent among both Individuals with IGD and those with attention deficit hyperactivity disorder (ADHD), the most comorbid psychiatric disorder of IGD. This study aimed to evaluate the relationships between circadian typologies, insomnia, and internet gaming disorder (IGD) and how ADHD affects this relationship. We recruited three groups of 69 young adults: an IGD group, a control group comprising age- and sex-matched nongamers, and a group of gamers without IGD through diagnostic interviews. The participants with IGD exhibited lower composite scale of morningness (CSM) scores and thus a higher eveningness preference In addition, the score of Pittsburgh insomnia rating scale-20-item version (PIRS_20) was significantly higher among those with IGD. The participants with IGD and ADHD exhibited lower CSM scores but higher PRIS_20 scores than the participants with IGD but without ADHD. The present findings indicate that participants with IGD exhibited a tendency of eveningness preference and experienced more severe insomnia. ADHD exacerbated the eveningness preference and insomnia of individuals with IGD. Close attention should be paid to sleep problems in individuals with IGD, particularly to those with ADHD.

A flagellin-conjugate protein induces dual NLRC4- and NLRP3-inflammasome activation which modulates inflammatory cytokine secretion from macrophages.

Background: A recombinant fusion protein combining the adjuvant and TLR5-ligand flagellin with the major birch pollen allergen Bet v 1 (rFlaA:Betv1) has been suggested to prevent the manifestation of birch allergy. Noteworthy, rFlaA:Betv1 induced both pro- and anti-inflammatory responses which were differentially regulated. However, the mechanism by which flagellin fusion proteins modulate allergen-specific immune responses, especially the mechanisms underlying IL-1ß secretion and their contribution to the overall immune responses remains elusive. Objective: To investigate the mechanisms underlying the production of IL-1ß from rFlaA:Betv1 stimulated macrophages. Methods: Macrophages were derived from mouse peritoneal-, human buffy-coat-, and PMA-differentiated THP-1 (wild type or lacking either ASC, NLRP3, or NLRC4) cells. Macrophages were stimulated with non-modified rFlaA:Betv1, mutant variants lacking either the flagellin DC0 domain or a sequence motif formerly described to mediate TLR5-activation, and respective controls in the presence or absence of inhibitors interfering with MAPK- and NFκB-signaling. Cytokine secretion was analyzed by ELISA and intracellular signaling by Western Blot. To study the contribution of IL-1ß to the overall immune responses, IL1R-deficient mouse peritoneal macrophages were used. Results: rFlaA:Betv1 consistently activated all types of investigated macrophages, inducing higher IL-1ß secretion compared with the equimolar mixture of both proteins. rFlaA:Betv1-induced activation of THP-1 macrophages was shown to be independent of either the TLR5-activating sequence motif or the flagellin DC0 domain but depended on both NLRP3- and NLRC4-inflammasomes. In addition, NFκB and SAP/JNK MAP kinases regulated rFlaA:Betv1-induced inflammasome activation and cytokine secretion by modulating pro-Caspase-1- and pro-IL-1ß-expression in THP-1 macrophages. Finally, lack of IL-1ß positive feedback via the IL1R strongly diminished the rFlaA:Betv1-induced secretion of IL-1ß, IL-6, and TNF-α from peritoneal macrophages. Conclusion: The mechanisms contributing to rFlaA:Betv1-induced IL-1ß secretion from macrophages were shown to be complex, involving both NLRC4- and NLRP3-inflammsomes, as well as NFκB- and SAP/JNK MAP kinase-signaling. Better understanding the mechanisms regulating the activation of immune cells by novel therapeutic candidates like the rFlaA:Betv1 fusion protein will allow us to further improve and develop new treatment strategies when using flagellin as an adjuvant.

Van der Waals Heterostructure Mid-Infrared Emitters with Electrically Controllable Polarization States and Spectral Characteristics.

Modern infrared (IR) microscopy, communication, and sensing systems demand control of the spectral characteristics and polarization states of light. Typically, these systems require the cascading of multiple filters, polarization optics, and rotating components to manipulate light, inevitably increasing their sizes and complexities. Here, we report two-terminal mid-infrared (mid-IR) emitters, in which tuning the polarity of the applied bias can switch their emission peak wavelengths and linear polarization states along two orthogonal orientations. Our devices are composed of two back-to-back p-n junctions formed by stacking anisotropic light-emitting materials, black phosphorus and black arsenic-phosphorus with MoS2. By controlling the crystallographic orientations and engineering the band profile of heterostructures, the emissions of two junctions exhibit distinct spectral ranges and polarization directions; more importantly, these two electroluminescence (EL) units can be independently activated, depending on the polarity of the applied bias. Furthermore, we show that when operating our emitter under the polarity-switched pulse mode, the time-averaged EL exhibits the characteristics of broad spectral coverage, encompassing the entire first mid-IR atmospheric window (λ: 3-5 µm), and electrically tunable spectral shapes.

Massively Concurrent Sub-Cellular Traction Force Videography enabled by Single-Pixel Optical Tracers (SPOTs).

We report a large field-of-view and high-speed videography platform for measuring the sub-cellular traction forces of more than 10,000 biological cells over 13mm 2 at 83 frames per second. Our Single-Pixel Optical Tracers (SPOT) tool uses 2-dimensional diffraction gratings embedded into a soft substrate to convert cells' mechanical traction stress into optical colors detectable by a video camera. The platform measures the sub-cellular traction forces of diverse cell types, including tightly connected tissue sheets and near isolated cells. We used this platform to explore the mechanical wave propagation in a tightly connected sheet of Neonatal Rat Ventricular Myocytes (NRVMs) and discovered that the activation time of some tissue regions are heterogeneous from the overall spiral wave behavior of the cardiac wave. One-Sentence Summary: An optical platform for fast, concurrent measurements of cell mechanics at 83 frames per second, over a large area of 13mm 2 .

A Chinese version of the Caring Assessment Report Evaluation Q-sort scale for measuring patients' perception on nurses' caring behaviours: reliability and validity assessment.

A reliable and valid instrument for understanding patients' perceptions of nurses' caring behaviour as well as assessing the quality of nursing care is necessary. The purpose of this study was to assess the reliability and validity of a Chinese version of the Caring Assessment Report Evaluation Q-sort (CARE-Q) Scale for the measurement of patients' perceptions of nurses' caring behaviours. The study sample comprised 250 patients from a medical centre in central Taiwan. Content validity, construct validity, internal consistency and stability reliability were assessed. The Content Validity Index of the Chinese version of CARE-Q was 0.90. Cronbach's alpha indicated good internal consistency reliability. Stability reliabilities for the six subscales ranged from 0.83 to 0.92. The results reveal that the Chinese version of the CARE-Q scale for the measurement of patients' perceptions on nurses' caring behaviours indicates high reliability (internal consistency and stability) and good content validity.